Intratumoral injection of dendritic cells transduced by an SV40-based vector expressing interleukin-15 induces curative immunity mediated by CD8+ T lymphocytes and NK cells
Cancer immunotherapy has been extensively attempted by gene transfer of cytokines with viral vectors. In this work, we compared the therapeutic effects of interleukin 12 and 15 (IL-12 and IL-15) genes transferred to tumor cells or to dendritic cells (DCs), which were subsequently injected into estab...
| Autores: | , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2005 |
| País: | España |
| Institución: | Universidad de Navarra |
| Repositorio: | Dadun. Depósito Académico Digital de la Universidad de Navarra |
| Idioma: | inglés |
| OAI Identifier: | oai:dadun.unav.edu:10171/21804 |
| Acceso en línea: | https://hdl.handle.net/10171/21804 |
| Access Level: | acceso abierto |
| Palabra clave: | SV40 Gene therapy Dendritic cells IL-15 IL-12 Colon carcinoma CT26 cells |
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Intratumoral injection of dendritic cells transduced by an SV40-based vector expressing interleukin-15 induces curative immunity mediated by CD8+ T lymphocytes and NK cellsVera, M. (María)|||/items/8f8ce09a-134e-4bcb-9c35-f04d2477d385Razquin, N. (Nerea)|||/items/b59c7d85-e337-4aa0-bf68-ad9aaa54009dPrieto, J. (Jesús)|||/items/0d9c3dec-4a09-400d-8c83-23ece1096c71Melero, I. (Ignacio)|||/items/82113ea8-7ce1-49d5-9ee3-42cf20db1c4eFortes, P. (Puri)|||/items/4b719a39-983d-402a-bb2a-2bdd276be18eGonzález-Aseguinolaza, G. (Gloria)|||/items/cb28732d-02bf-4339-ab60-ff738ee191acSV40Gene therapyDendritic cellsIL-15IL-12Colon carcinoma CT26 cellsCancer immunotherapy has been extensively attempted by gene transfer of cytokines with viral vectors. In this work, we compared the therapeutic effects of interleukin 12 and 15 (IL-12 and IL-15) genes transferred to tumor cells or to dendritic cells (DCs), which were subsequently injected into established tumors. For this purpose, we used viral vectors based on simian virus 40 (rSV40). Importantly, we observed that nonmatured DCs infected with rSV40 vectors remained phenotypically immature. Infection of CT-26 tumor cells with rSV40 expressing IL-12 (rSVIL-12) or IL-15 (rSVIL-15) failed to inhibit tumor development. In contrast, the intratumoral administration of syngeneic DCs transduced with rSVIL-12 or rSVIL-15 was associated with a strong antitumor response; up to 40% tumor remissions were achieved with DCs transduced by rSVIL-12 and 73% with DCs expressing IL-15. This antitumor effect correlated with the in vivo priming of tumor-specific CD8+ T lymphocytes. Depletion studies showed that rSVIL-15-mediated antitumor efficacy was mediated mainly by CD8+ T lymphocytes and NK cells. We conclude that (i) SV40-derived vectors are an advantageous alternative to transduce genes into DCs and (ii) DCs transferred with IL-15 have an enhanced capability to induce curative antitumor immunity when injected into malignant lesions.Nature Publishing GroupDadun. Depósito Académico Digital Universidad de Navarra20122012-04-2620052005-01-0120052005-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/21804reponame:Dadun. Depósito Académico Digital de la Universidad de Navarrainstname:Universidad de NavarraInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:dadun.unav.edu:10171/218042026-06-21T12:47:57Z |
| dc.title.none.fl_str_mv |
Intratumoral injection of dendritic cells transduced by an SV40-based vector expressing interleukin-15 induces curative immunity mediated by CD8+ T lymphocytes and NK cells |
| title |
Intratumoral injection of dendritic cells transduced by an SV40-based vector expressing interleukin-15 induces curative immunity mediated by CD8+ T lymphocytes and NK cells |
| spellingShingle |
Intratumoral injection of dendritic cells transduced by an SV40-based vector expressing interleukin-15 induces curative immunity mediated by CD8+ T lymphocytes and NK cells Vera, M. (María)|||/items/8f8ce09a-134e-4bcb-9c35-f04d2477d385 SV40 Gene therapy Dendritic cells IL-15 IL-12 Colon carcinoma CT26 cells |
| title_short |
Intratumoral injection of dendritic cells transduced by an SV40-based vector expressing interleukin-15 induces curative immunity mediated by CD8+ T lymphocytes and NK cells |
| title_full |
Intratumoral injection of dendritic cells transduced by an SV40-based vector expressing interleukin-15 induces curative immunity mediated by CD8+ T lymphocytes and NK cells |
| title_fullStr |
Intratumoral injection of dendritic cells transduced by an SV40-based vector expressing interleukin-15 induces curative immunity mediated by CD8+ T lymphocytes and NK cells |
| title_full_unstemmed |
Intratumoral injection of dendritic cells transduced by an SV40-based vector expressing interleukin-15 induces curative immunity mediated by CD8+ T lymphocytes and NK cells |
| title_sort |
Intratumoral injection of dendritic cells transduced by an SV40-based vector expressing interleukin-15 induces curative immunity mediated by CD8+ T lymphocytes and NK cells |
| dc.creator.none.fl_str_mv |
Vera, M. (María)|||/items/8f8ce09a-134e-4bcb-9c35-f04d2477d385 Razquin, N. (Nerea)|||/items/b59c7d85-e337-4aa0-bf68-ad9aaa54009d Prieto, J. (Jesús)|||/items/0d9c3dec-4a09-400d-8c83-23ece1096c71 Melero, I. (Ignacio)|||/items/82113ea8-7ce1-49d5-9ee3-42cf20db1c4e Fortes, P. (Puri)|||/items/4b719a39-983d-402a-bb2a-2bdd276be18e González-Aseguinolaza, G. (Gloria)|||/items/cb28732d-02bf-4339-ab60-ff738ee191ac |
| author |
Vera, M. (María)|||/items/8f8ce09a-134e-4bcb-9c35-f04d2477d385 |
| author_facet |
Vera, M. (María)|||/items/8f8ce09a-134e-4bcb-9c35-f04d2477d385 Razquin, N. (Nerea)|||/items/b59c7d85-e337-4aa0-bf68-ad9aaa54009d Prieto, J. (Jesús)|||/items/0d9c3dec-4a09-400d-8c83-23ece1096c71 Melero, I. (Ignacio)|||/items/82113ea8-7ce1-49d5-9ee3-42cf20db1c4e Fortes, P. (Puri)|||/items/4b719a39-983d-402a-bb2a-2bdd276be18e González-Aseguinolaza, G. (Gloria)|||/items/cb28732d-02bf-4339-ab60-ff738ee191ac |
| author_role |
author |
| author2 |
Razquin, N. (Nerea)|||/items/b59c7d85-e337-4aa0-bf68-ad9aaa54009d Prieto, J. (Jesús)|||/items/0d9c3dec-4a09-400d-8c83-23ece1096c71 Melero, I. (Ignacio)|||/items/82113ea8-7ce1-49d5-9ee3-42cf20db1c4e Fortes, P. (Puri)|||/items/4b719a39-983d-402a-bb2a-2bdd276be18e González-Aseguinolaza, G. (Gloria)|||/items/cb28732d-02bf-4339-ab60-ff738ee191ac |
| author2_role |
author author author author author |
| dc.contributor.none.fl_str_mv |
Dadun. Depósito Académico Digital Universidad de Navarra |
| dc.subject.none.fl_str_mv |
SV40 Gene therapy Dendritic cells IL-15 IL-12 Colon carcinoma CT26 cells |
| topic |
SV40 Gene therapy Dendritic cells IL-15 IL-12 Colon carcinoma CT26 cells |
| description |
Cancer immunotherapy has been extensively attempted by gene transfer of cytokines with viral vectors. In this work, we compared the therapeutic effects of interleukin 12 and 15 (IL-12 and IL-15) genes transferred to tumor cells or to dendritic cells (DCs), which were subsequently injected into established tumors. For this purpose, we used viral vectors based on simian virus 40 (rSV40). Importantly, we observed that nonmatured DCs infected with rSV40 vectors remained phenotypically immature. Infection of CT-26 tumor cells with rSV40 expressing IL-12 (rSVIL-12) or IL-15 (rSVIL-15) failed to inhibit tumor development. In contrast, the intratumoral administration of syngeneic DCs transduced with rSVIL-12 or rSVIL-15 was associated with a strong antitumor response; up to 40% tumor remissions were achieved with DCs transduced by rSVIL-12 and 73% with DCs expressing IL-15. This antitumor effect correlated with the in vivo priming of tumor-specific CD8+ T lymphocytes. Depletion studies showed that rSVIL-15-mediated antitumor efficacy was mediated mainly by CD8+ T lymphocytes and NK cells. We conclude that (i) SV40-derived vectors are an advantageous alternative to transduce genes into DCs and (ii) DCs transferred with IL-15 have an enhanced capability to induce curative antitumor immunity when injected into malignant lesions. |
| publishDate |
2005 |
| dc.date.none.fl_str_mv |
2005 2005-01-01 2005 2005-01-01 2012 2012-04-26 |
| dc.type.none.fl_str_mv |
journal article http://purl.org/coar/resource_type/c_6501 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/10171/21804 |
| url |
https://hdl.handle.net/10171/21804 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 |
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info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
open access http://purl.org/coar/access_right/c_abf2 |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.publisher.none.fl_str_mv |
Nature Publishing Group |
| publisher.none.fl_str_mv |
Nature Publishing Group |
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reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra instname:Universidad de Navarra |
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Universidad de Navarra |
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Dadun. Depósito Académico Digital de la Universidad de Navarra |
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Dadun. Depósito Académico Digital de la Universidad de Navarra |
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15.300719 |